Anaplastic Large Cell Lymphoma and Breast Implants? A Review of the Literature

1. Anaplastic Large Cell Lymphoma and Breast Implants? A Review of the Literature G. Patrick Maxwell1, Joan Largent2, Michael G. Oefelein2 1Maxwell Aesthetics, Nashville, TN; 2Allergan Inc., Irvine, CA Disclosures G. Patrick Maxwell is a Consultant for Allergan, Inc. Joan Largent and Michael G. Oefelein are Employees of Allergan, Inc.

2. ABSTRACT Purpose:. We aimed to review the available evidence on Anaplastic Large Cell Lymphoma (ALCL) and breast implants (BI) including case reports and epidemiologic studies, and provide a critical evaluation. Methods: Search methods: i) Database=PubMed; ii) Search terms=”breast implant” and “lymphoma”, or “primary breast lymphoma” or “primary T-cell breast lymphoma” or “breast implant and ALCL”; iii) Inclusion criteria: language=English; human studies; iv) Expand search based on review of references. Results:ALCL is a rare, aggressive T-cell lymphoma characterized by the uniform expression of the CD30 antigen, with the majority of cases also positive for aplastic lymphoma kinase (ALK). ALCL can be either cutaneous or systemic. A review of the literature for reports of ALCL in breast implant recipients revealed a total of 15 published reports describing a total of 25 patients with ALCL in patients with silicone gel-filled or saline-filled breast implants (1 July 2010). Additional findings were: 1) Breast-ALCL has been reported in women with and without BI [5,6] and, 2) with and without a prior cancer history [18]. The only case-control study examining an association between ALCL and BI to date [6] included 6/11 ALK-negative ALCL cases with no history of BI . Nine of 25 (36%) ALCL cases reported among patients with BI had a personal history of breast cancer (N=8) or lymphoma (N=1) [18]. 3) Authors concluded ALCL in the anecdotal case reports behaves indolently, and spontaneous resolutions have been reported; however, most patients with ALCL received chemotherapy and/or radiotherapy [24]. 4) Device type in case reports is often unknown [18]; reports have included saline- and silicone-filled devices [18]. 5) Interval between implantation and ALCL diagnosis varies widely in the reports, between 1-23 years [6]. 6) Primary breast lymphomas may be difficult to definitively diagnose and distinguish from secondary involvement of disease originating elsewhere [8]. Five of 11 ALCL cases in the case-control study had disseminated disease with involvement of other sites providing uncertainty about the breast as the primary site [6]. 7) BI patients have been reported to have demographic and lifestyle characteristics which may influence their risk of certain cancers [3]; the relevance of these characteristics to ALCL risk is unknown. 8) While no prospective epidemiologic studies have examined ALCL risk among BI patients to date, several have reported no significantly increased NHL risk [19]. Conclusions: Overall, the evidence regarding a BI- ALCL association is inconclusive.

3. OBJECTIVE We aimed to review the available evidence on Anaplastic Large Cell Lymphoma (ALCL) and breast implants (BI) including case reports and epidemiologic studies, and provide a critical evaluation.

4. METHODS To identify cases of breast-associated ALCL, a PubMed search limited to English language, human studies was conducted using search terms ”breast implant” and “lymphoma”, “primary breast lymphoma” or “primary T-cell breast lymphoma” or “breast implant and ALCL”. Additional references of relevance were identified from the reference lists of retrieved publications.

5. RESULTS Table 1: Summary of cases in the literature of anaplastic large T-cell lymphoma in patients with breast implants ALK, anaplastic lymphoma kinase; LN, lymph node; NA, not available

6. Table 1 (Continued) ALK, anaplastic lymphoma kinase; LN, lymph node; NA, not available

7. RESULTS Table 2: Summary of literature cases of anaplastic large T-cell lymphoma in patients with breast implants ALCL, anaplastic large T-cell lymphoma; NA, not available

8. CONCLUSIONS The evidence to date regarding a causal association between breast implants and ALCL is inconclusive and deserves further rigorous scientific study to elucidate: 1) potential cause and effect; 2) proper disease classification; 3) Heterogeneous clinical course, 4) relevance of prior cancer and/or cancer treatment; 5) relevance of late seroma 6) extremely rare occurrence.

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